SummaryAllocation Made PracticaL
The AMPLify project will lay the foundations of a new field, computational behavioural game theory that brings a computational perspective, computational implementation, and behavioural insights to game theory. These foundations will be laid by tackling a pressing problem facing society today: the efficient and fair allocation of resources and costs. Research in allocation has previously considered simple, abstract models like cake cutting. We propose to develop richer models that capture important new features like asynchronicity which occur in many markets being developed in our highly connected and online world. The mechanisms currently used to allocate resources and costs are limited to these simple, abstract models and also do not take into account how people actually behave in practice. We will therefore design new mechanisms for these richer allocation problems that exploit insights gained from behavioural game theory like loss aversion. We will also tackle the complexity of these rich models and mechanisms with computational tools. Finally, we will use computation to increase both the efficiency and fairness of allocations. As a result, we will be able to do more with fewer resources and greater fairness. Our initial case studies in resource and cost allocation demonstrate that we can improve efficiency greatly, offering one company alone savings of up to 10% (which is worth tens of millions of dollars every year). We predict even greater impact with the more sophisticated mechanisms to be developed during the course of this project.

Allocation Made PracticaL
The AMPLify project will lay the foundations of a new field, computational behavioural game theory that brings a computational perspective, computational implementation, and behavioural insights to game theory. These foundations will be laid by tackling a pressing problem facing society today: the efficient and fair allocation of resources and costs. Research in allocation has previously considered simple, abstract models like cake cutting. We propose to develop richer models that capture important new features like asynchronicity which occur in many markets being developed in our highly connected and online world. The mechanisms currently used to allocate resources and costs are limited to these simple, abstract models and also do not take into account how people actually behave in practice. We will therefore design new mechanisms for these richer allocation problems that exploit insights gained from behavioural game theory like loss aversion. We will also tackle the complexity of these rich models and mechanisms with computational tools. Finally, we will use computation to increase both the efficiency and fairness of allocations. As a result, we will be able to do more with fewer resources and greater fairness. Our initial case studies in resource and cost allocation demonstrate that we can improve efficiency greatly, offering one company alone savings of up to 10% (which is worth tens of millions of dollars every year). We predict even greater impact with the more sophisticated mechanisms to be developed during the course of this project.

SummaryThe project outlined here addresses the fundamental question how the brain encodes and controls behavior. While we have a reasonable understanding of the role of entire brain areas in such processes, and of mechanisms at the molecular and synaptic levels, there is a big gap in our knowledge of how behavior is controlled at the level of defined neuronal circuits.
In natural environments, chances for survival depend on learning about possible aversive and appetitive outcomes and on the appropriate behavioral responses. Most studies addressing the underlying mechanisms at the level of neuronal circuits have focused on aversive learning, such as in Pavlovian fear conditioning. Understanding how activity in defined neuronal circuits mediates appetitive learning, as well as how these circuitries are shared and interact with aversive learning circuits, is a central question in the neuroscience of learning and memory and the focus of this grant application.
Using a multidisciplinary approach in mice, combining behavioral, in vivo and in vitro electrophysiological, imaging, optogenetic and state-of-the-art viral circuit tracing techniques, we aim at dissecting the neuronal circuitry of appetitive Pavlovian conditioning with a focus on the amygdala, a key brain region important for both aversive and appetitive learning. Ultimately, elucidating these mechanisms at the level of defined neurons and circuits is fundamental not only for an understanding of memory processes in the brain in general, but also to inform a mechanistic approach to psychiatric conditions associated with amygdala dysfunction and dysregulated emotional responses including anxiety and mood disorders.

The project outlined here addresses the fundamental question how the brain encodes and controls behavior. While we have a reasonable understanding of the role of entire brain areas in such processes, and of mechanisms at the molecular and synaptic levels, there is a big gap in our knowledge of how behavior is controlled at the level of defined neuronal circuits.
In natural environments, chances for survival depend on learning about possible aversive and appetitive outcomes and on the appropriate behavioral responses. Most studies addressing the underlying mechanisms at the level of neuronal circuits have focused on aversive learning, such as in Pavlovian fear conditioning. Understanding how activity in defined neuronal circuits mediates appetitive learning, as well as how these circuitries are shared and interact with aversive learning circuits, is a central question in the neuroscience of learning and memory and the focus of this grant application.
Using a multidisciplinary approach in mice, combining behavioral, in vivo and in vitro electrophysiological, imaging, optogenetic and state-of-the-art viral circuit tracing techniques, we aim at dissecting the neuronal circuitry of appetitive Pavlovian conditioning with a focus on the amygdala, a key brain region important for both aversive and appetitive learning. Ultimately, elucidating these mechanisms at the level of defined neurons and circuits is fundamental not only for an understanding of memory processes in the brain in general, but also to inform a mechanistic approach to psychiatric conditions associated with amygdala dysfunction and dysregulated emotional responses including anxiety and mood disorders.

SummaryThis project is a comparative anthropology of conscience, ethics and human rights. Numerous international human rights documents formally declare their commitment to protect freedom of conscience. But, what is conscience and how do we know it when we see it? How do we distinguish it from self-interest or fanaticism? And what happens when the concept, often associated with a distinct Christian or liberal history, travels across cultural boundaries? The project will examine the cultural conditions under which claims to conscience are made possible, and the types of claims that are most persuasive when doing so. The project addresses these issues through the comparative analysis of three case studies: British pacifists, Sri Lankan activists, and Soviet dissidents. These case studies have been carefully chosen to provide globally significant, but contrasting examples of contests over the implications of claims to conscience. If claims of conscience are often associated with a specifically liberal and Christian tradition, mid-twentieth century Britain can be said to stand at the centre of that tradition. Sri Lanka represents a particularly fraught post-colonial South Asian counterpoint, wracked by nationalist violence, and influenced by ethical traditions associated with forms of Hinduism and Buddhism. Soviet Russia represents a further contrast, a totalitarian regime, where atheism was the dominant ethical language. Finally, the project will return specifically to international human rights institutions, examining the history of the category of conscience in the UN human rights system. This project will be ground breaking, employing novel methods and analytical insights, in order to producing the first comparative analysis of the cultural and political salience of claims of conscience. In doing so, the research aims to transform our understandings of the limits and potentials of attempts to protect freedom of conscience.

This project is a comparative anthropology of conscience, ethics and human rights. Numerous international human rights documents formally declare their commitment to protect freedom of conscience. But, what is conscience and how do we know it when we see it? How do we distinguish it from self-interest or fanaticism? And what happens when the concept, often associated with a distinct Christian or liberal history, travels across cultural boundaries? The project will examine the cultural conditions under which claims to conscience are made possible, and the types of claims that are most persuasive when doing so. The project addresses these issues through the comparative analysis of three case studies: British pacifists, Sri Lankan activists, and Soviet dissidents. These case studies have been carefully chosen to provide globally significant, but contrasting examples of contests over the implications of claims to conscience. If claims of conscience are often associated with a specifically liberal and Christian tradition, mid-twentieth century Britain can be said to stand at the centre of that tradition. Sri Lanka represents a particularly fraught post-colonial South Asian counterpoint, wracked by nationalist violence, and influenced by ethical traditions associated with forms of Hinduism and Buddhism. Soviet Russia represents a further contrast, a totalitarian regime, where atheism was the dominant ethical language. Finally, the project will return specifically to international human rights institutions, examining the history of the category of conscience in the UN human rights system. This project will be ground breaking, employing novel methods and analytical insights, in order to producing the first comparative analysis of the cultural and political salience of claims of conscience. In doing so, the research aims to transform our understandings of the limits and potentials of attempts to protect freedom of conscience.

SummaryThe skeleton and the sinusoidal vasculature form a functional unit with great relevance in health, regeneration, and disease. Currently, fundamental aspects of sinusoidal vessel growth, specialization, arteriovenous organization and the consequences for tissue perfusion, or the changes occurring during ageing remain unknown. Our preliminary data indicate that key principles of bone vascularization and the role of molecular regulators are highly distinct from other organs. I therefore propose to use powerful combination of mouse genetics, fate mapping, transcriptional profiling, computational biology, confocal and two-photon microscopy, micro-CT and PET imaging, biochemistry and cell biology to characterize the growth, differentiation, dynamics, and ageing of the bone vasculature. In addition to established angiogenic pathways, the role of highly promising novel candidate regulators will be investigated in endothelial cells and perivascular osteoprogenitors with sophisticated inducible and cell type-specific genetic methods in the mouse. Complementing these powerful in vivo approaches, 3D co-cultures generated by cell printing technologies will provide insight into the communication between different cell types. The dynamics of sinusoidal vessel growth and regeneration will be monitored by two-photon imaging in the skull. Finally, I will explore the architectural, cellular and molecular changes and the role of capillary endothelial subpopulations in the sinusoidal vasculature of ageing and osteoporotic mice.
Technological advancements, such as new transgenic strains, mutant models or cell printing approaches, are important aspects of this proposal. AngioBone will provide a first conceptual framework for normal and deregulated function of the bone sinusoidal vasculature. It will also break new ground by analyzing the role of blood vessels in ageing and identifying novel strategies for tissue engineering and, potentially, the prevention/treatment of osteoporosis.

The skeleton and the sinusoidal vasculature form a functional unit with great relevance in health, regeneration, and disease. Currently, fundamental aspects of sinusoidal vessel growth, specialization, arteriovenous organization and the consequences for tissue perfusion, or the changes occurring during ageing remain unknown. Our preliminary data indicate that key principles of bone vascularization and the role of molecular regulators are highly distinct from other organs. I therefore propose to use powerful combination of mouse genetics, fate mapping, transcriptional profiling, computational biology, confocal and two-photon microscopy, micro-CT and PET imaging, biochemistry and cell biology to characterize the growth, differentiation, dynamics, and ageing of the bone vasculature. In addition to established angiogenic pathways, the role of highly promising novel candidate regulators will be investigated in endothelial cells and perivascular osteoprogenitors with sophisticated inducible and cell type-specific genetic methods in the mouse. Complementing these powerful in vivo approaches, 3D co-cultures generated by cell printing technologies will provide insight into the communication between different cell types. The dynamics of sinusoidal vessel growth and regeneration will be monitored by two-photon imaging in the skull. Finally, I will explore the architectural, cellular and molecular changes and the role of capillary endothelial subpopulations in the sinusoidal vasculature of ageing and osteoporotic mice.
Technological advancements, such as new transgenic strains, mutant models or cell printing approaches, are important aspects of this proposal. AngioBone will provide a first conceptual framework for normal and deregulated function of the bone sinusoidal vasculature. It will also break new ground by analyzing the role of blood vessels in ageing and identifying novel strategies for tissue engineering and, potentially, the prevention/treatment of osteoporosis.

Host Institution (HI)UNIVERSITY COLLEGE CORK - NATIONAL UNIVERSITY OF IRELAND, CORK

Call DetailsStarting Grant (StG), LS8, ERC-2014-STG

SummaryWhat does the fossil record tell us about the evolution of colour in animals through deep time? Evidence of colour in fossils can inform on the visual signalling strategies used by ancient animals. Research to date often has a narrow focus, lacks a broad phylogenetic and temporal context, and rarely incorporates information on taphonomy. This proposal represents a bold new holistic approach to the study of fossil colour: it will couple powerful imaging- and chemical analytical techniques with a rigorous programme of fossilisation experiments simulating decay, burial, and transport, and analysis of fossils and their sedimentary context, to construct the first robust models for the evolution of colour in animals through deep time. The research will resolve the original integumentary colours of fossil higher vertebrates, and the original colours of fossil hair; the fossil record of non-melanin pigments in feathers and insects; the biological significance of monotonal patterning in fossil insects; and the evolutionary history of scales and 3D photonic crystals in insects. Critically, the research will test, for the first time, whether evidence of fossil colour can solve broader evolutionary questions, e.g. the true affinities of enigmatic Cambrian chordate-like metazoans, and feather-like integumentary filaments in dinosaurs. The proposal entails construction of a dedicated experimental maturation laboratory for simulating the impact of burial on tissues. This laboratory will form the core of the world’s first integrated ‘experimental fossilisation facility’, consolidating the PI’s team as the global hub for fossil colour research. The research team comprises the PI, three postdoctoral researchers, and three PhD students, and will form an extensive research network via collaborations with 13 researchers from Europe and beyond. The project will reach out to diverse scientists and will inspire a positive attitude to science among the general public and policymakers alike.

What does the fossil record tell us about the evolution of colour in animals through deep time? Evidence of colour in fossils can inform on the visual signalling strategies used by ancient animals. Research to date often has a narrow focus, lacks a broad phylogenetic and temporal context, and rarely incorporates information on taphonomy. This proposal represents a bold new holistic approach to the study of fossil colour: it will couple powerful imaging- and chemical analytical techniques with a rigorous programme of fossilisation experiments simulating decay, burial, and transport, and analysis of fossils and their sedimentary context, to construct the first robust models for the evolution of colour in animals through deep time. The research will resolve the original integumentary colours of fossil higher vertebrates, and the original colours of fossil hair; the fossil record of non-melanin pigments in feathers and insects; the biological significance of monotonal patterning in fossil insects; and the evolutionary history of scales and 3D photonic crystals in insects. Critically, the research will test, for the first time, whether evidence of fossil colour can solve broader evolutionary questions, e.g. the true affinities of enigmatic Cambrian chordate-like metazoans, and feather-like integumentary filaments in dinosaurs. The proposal entails construction of a dedicated experimental maturation laboratory for simulating the impact of burial on tissues. This laboratory will form the core of the world’s first integrated ‘experimental fossilisation facility’, consolidating the PI’s team as the global hub for fossil colour research. The research team comprises the PI, three postdoctoral researchers, and three PhD students, and will form an extensive research network via collaborations with 13 researchers from Europe and beyond. The project will reach out to diverse scientists and will inspire a positive attitude to science among the general public and policymakers alike.

SummaryComputer animation has traditionally been associated with applications in virtual-reality-based training, video games or feature films. However, interactive animation is gaining relevance in a more general scope, as a tool for early-stage analysis, design and planning in many applications in science and engineering. The user can get quick and visual feedback of the results, and then proceed by refining the experiments or designs. Potential applications include nanodesign, e-commerce or tactile telecommunication, but they also reach as far as, e.g., the analysis of ecological, climate, biological or physiological processes.
The application of computer animation is extremely limited in comparison to its potential outreach due to a trade-off between accuracy and computational efficiency. Such trade-off is induced by inherent complexity sources such as nonlinear or anisotropic behaviors, heterogeneous properties, or high dynamic ranges of effects.
The Animetrics project proposes a modeling and animation methodology, which consists of a multi-scale decomposition of complex processes, the description of the process at each scale through combination of simple local models, and fitting the parameters of those local models using large amounts of data from example effects. The modeling and animation methodology will be explored on specific problems arising in complex mechanical phenomena, including viscoelasticity of solids and thin shells, multi-body contact, granular and liquid flow, and fracture of solids.

Computer animation has traditionally been associated with applications in virtual-reality-based training, video games or feature films. However, interactive animation is gaining relevance in a more general scope, as a tool for early-stage analysis, design and planning in many applications in science and engineering. The user can get quick and visual feedback of the results, and then proceed by refining the experiments or designs. Potential applications include nanodesign, e-commerce or tactile telecommunication, but they also reach as far as, e.g., the analysis of ecological, climate, biological or physiological processes.
The application of computer animation is extremely limited in comparison to its potential outreach due to a trade-off between accuracy and computational efficiency. Such trade-off is induced by inherent complexity sources such as nonlinear or anisotropic behaviors, heterogeneous properties, or high dynamic ranges of effects.
The Animetrics project proposes a modeling and animation methodology, which consists of a multi-scale decomposition of complex processes, the description of the process at each scale through combination of simple local models, and fitting the parameters of those local models using large amounts of data from example effects. The modeling and animation methodology will be explored on specific problems arising in complex mechanical phenomena, including viscoelasticity of solids and thin shells, multi-body contact, granular and liquid flow, and fracture of solids.

Summary"During the past twenty years, we have witnessed profound technological changes, summarised under the terms of digital revolution or entering the information age. It is evident that these technological changes will have a deep societal impact, and questions of privacy and security are primordial to ensure the survival of a free and open society.
Cryptology is a main building block of any security solution, and at the heart of projects such as electronic identity and health cards, access control, digital content distribution or electronic voting, to mention only a few important applications. During the past decades, public-key cryptology has established itself as a research topic in computer science; tools of theoretical computer science are employed to “prove” the security of cryptographic primitives such as encryption or digital signatures and of more complex protocols. It is often forgotten, however, that all practically relevant public-key cryptosystems are rooted in pure mathematics, in particular, number theory and arithmetic geometry. In fact, the socalled security “proofs” are all conditional to the algorithmic untractability of certain number theoretic problems, such as factorisation of large integers or discrete logarithms in algebraic curves. Unfortunately, there is a large cultural gap between computer scientists using a black-box security reduction to a supposedly hard problem in algorithmic number theory and number theorists, who are often interested in solving small and easy instances of the same problem. The theoretical grounds on which current algorithmic number theory operates are actually rather shaky, and cryptologists are generally unaware of this fact.
The central goal of ANTICS is to rebuild algorithmic number theory on the firm grounds of theoretical computer science."

"During the past twenty years, we have witnessed profound technological changes, summarised under the terms of digital revolution or entering the information age. It is evident that these technological changes will have a deep societal impact, and questions of privacy and security are primordial to ensure the survival of a free and open society.
Cryptology is a main building block of any security solution, and at the heart of projects such as electronic identity and health cards, access control, digital content distribution or electronic voting, to mention only a few important applications. During the past decades, public-key cryptology has established itself as a research topic in computer science; tools of theoretical computer science are employed to “prove” the security of cryptographic primitives such as encryption or digital signatures and of more complex protocols. It is often forgotten, however, that all practically relevant public-key cryptosystems are rooted in pure mathematics, in particular, number theory and arithmetic geometry. In fact, the socalled security “proofs” are all conditional to the algorithmic untractability of certain number theoretic problems, such as factorisation of large integers or discrete logarithms in algebraic curves. Unfortunately, there is a large cultural gap between computer scientists using a black-box security reduction to a supposedly hard problem in algorithmic number theory and number theorists, who are often interested in solving small and easy instances of the same problem. The theoretical grounds on which current algorithmic number theory operates are actually rather shaky, and cryptologists are generally unaware of this fact.
The central goal of ANTICS is to rebuild algorithmic number theory on the firm grounds of theoretical computer science."

Max ERC Funding

1 453 507 €

Duration

Start date: 2012-01-01, End date: 2016-12-31

Project acronymAOC

ProjectAdversary-Oriented Computing

Researcher (PI)Rachid Guerraoui

Host Institution (HI)ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE

Call DetailsAdvanced Grant (AdG), PE6, ERC-2013-ADG

Summary"Recent technological evolutions, including the cloud, the multicore, the social and the mobiles ones, are turning computing ubiquitously distributed. Yet, building high-assurance distributed programs is notoriously challenging. One of the main reasons is that these systems usually seek to achieve several goals at the same time. In short, they need to be efficient, responding effectively in various average-case conditions, as well as reliable, behaving correctly in severe, worst-case conditions. As a consequence, they typically intermingle different strategies: each to cope with some specific condition, e.g., with or without node failures, message losses, time-outs, contention, cache misses,
over-sizing, malicious attacks, etc. The resulting programs end up hard to design, prove, verify, implement, test and debug. Not surprisingly, there are anecdotal evidences of the fragility of the most celebrated distributed systems.
The goal of this project is to contribute to building high-assurance distributed programs by introducing a new dimension for separating and isolating their concerns, as well as a new scheme for composing and reusing them in a modular manner. In short, the project will explore the inherent power and limitations of a novel paradigm, Adversary-Oriented Computing (AOC). Sub-programs, each implementing a specific strategy to cope with a given adversary, modelling a specific working condition, are designed, proved, verified, implemented, tested and debugged independently. They are then composed, possibly dynamically, as black-boxes within the same global program. The AOC project is ambitious and it seeks to fundamentally revisit the way distributed algorithms are designed and distributed systems are implemented. The gain expected in comparison with today's approaches is substantial, and I believe it will be proportional to the degree of difficulty of the distributed problem at hand."

"Recent technological evolutions, including the cloud, the multicore, the social and the mobiles ones, are turning computing ubiquitously distributed. Yet, building high-assurance distributed programs is notoriously challenging. One of the main reasons is that these systems usually seek to achieve several goals at the same time. In short, they need to be efficient, responding effectively in various average-case conditions, as well as reliable, behaving correctly in severe, worst-case conditions. As a consequence, they typically intermingle different strategies: each to cope with some specific condition, e.g., with or without node failures, message losses, time-outs, contention, cache misses,
over-sizing, malicious attacks, etc. The resulting programs end up hard to design, prove, verify, implement, test and debug. Not surprisingly, there are anecdotal evidences of the fragility of the most celebrated distributed systems.
The goal of this project is to contribute to building high-assurance distributed programs by introducing a new dimension for separating and isolating their concerns, as well as a new scheme for composing and reusing them in a modular manner. In short, the project will explore the inherent power and limitations of a novel paradigm, Adversary-Oriented Computing (AOC). Sub-programs, each implementing a specific strategy to cope with a given adversary, modelling a specific working condition, are designed, proved, verified, implemented, tested and debugged independently. They are then composed, possibly dynamically, as black-boxes within the same global program. The AOC project is ambitious and it seeks to fundamentally revisit the way distributed algorithms are designed and distributed systems are implemented. The gain expected in comparison with today's approaches is substantial, and I believe it will be proportional to the degree of difficulty of the distributed problem at hand."

Max ERC Funding

2 147 012 €

Duration

Start date: 2014-06-01, End date: 2019-05-31

Project acronymAPOLs

ProjectRole of Apolipoproteins L in immunity and disease

Researcher (PI)Etienne Pays

Host Institution (HI)UNIVERSITE LIBRE DE BRUXELLES

Call DetailsAdvanced Grant (AdG), LS6, ERC-2014-ADG

SummaryWork conducted in my laboratory on the trypanosome killing factor of human serum led to the identification
of the primate-specific Apolipoprotein L1 (APOL1) as a novel pore-forming protein with striking similarities
with proteins of the apoptotic BCL2 family. APOL1 belongs to a family of proteins induced under
inflammatory conditions in myeloid and endothelial cells. APOL1 is efficiently neutralized by the SRA
protein of Trypanosoma rhodesiense, accounting for the ability of this trypanosome subspecies to infect
humans and cause sleeping sickness. We found that natural APOL1 variants escaping SRA neutralization and
therefore conferring human resistance to T. rhodesiense are associated with chronic kidney disease.
Moreover, transgenic mice expressing these APOL1 variants exhibit an obese phenotype. Our unpublished
results also indicate that APOLs control the lifespan of dendritic cells and podocytes activated by viral
stimuli. Therefore, we propose that the pathology of APOL variants is due to their deregulated activity on the
control of the cellular lifespan in myeloid/endothelial cells activated by pathogen detection.
This project aims at characterizing (i) the molecular mechanism by which APOLs control the lifespan of
activated dendritic cells and podocytes, which has direct impact on innate immunity and inflammation, and
(ii) the mechanism by which APOL1 variants cause pathology. In addition, we plan to detail the
physiological function of APOLs by studying the phenotype of transgenic mice either expressing human
APOL1 (wild-type and variants) or devoid of APOL genes, which we have recently generated. Finally, we
propose to exploit the extraordinary potential of trypanosomes for antigenic variation in order to produce
SRA variants able to neutralize the pathogenic APOL1 variants. Preliminary experiments suggest that in
podocytes SRA antagonizes APOL1 induction by viral stimulus and subsequent cell death, opening new
perspectives to treat kidney disease.

Work conducted in my laboratory on the trypanosome killing factor of human serum led to the identification
of the primate-specific Apolipoprotein L1 (APOL1) as a novel pore-forming protein with striking similarities
with proteins of the apoptotic BCL2 family. APOL1 belongs to a family of proteins induced under
inflammatory conditions in myeloid and endothelial cells. APOL1 is efficiently neutralized by the SRA
protein of Trypanosoma rhodesiense, accounting for the ability of this trypanosome subspecies to infect
humans and cause sleeping sickness. We found that natural APOL1 variants escaping SRA neutralization and
therefore conferring human resistance to T. rhodesiense are associated with chronic kidney disease.
Moreover, transgenic mice expressing these APOL1 variants exhibit an obese phenotype. Our unpublished
results also indicate that APOLs control the lifespan of dendritic cells and podocytes activated by viral
stimuli. Therefore, we propose that the pathology of APOL variants is due to their deregulated activity on the
control of the cellular lifespan in myeloid/endothelial cells activated by pathogen detection.
This project aims at characterizing (i) the molecular mechanism by which APOLs control the lifespan of
activated dendritic cells and podocytes, which has direct impact on innate immunity and inflammation, and
(ii) the mechanism by which APOL1 variants cause pathology. In addition, we plan to detail the
physiological function of APOLs by studying the phenotype of transgenic mice either expressing human
APOL1 (wild-type and variants) or devoid of APOL genes, which we have recently generated. Finally, we
propose to exploit the extraordinary potential of trypanosomes for antigenic variation in order to produce
SRA variants able to neutralize the pathogenic APOL1 variants. Preliminary experiments suggest that in
podocytes SRA antagonizes APOL1 induction by viral stimulus and subsequent cell death, opening new
perspectives to treat kidney disease.

Summary"In plants, receptor kinases form the largest family of plasma membrane (PM) receptors and they are involved in virtually all aspects of the plant life, including development, immunity and reproduction. In animals, key molecules that orchestrate the recruitment of signaling proteins to membranes are anionic phospholipids (e.g. phosphatidylinositol phosphate or PIPs). Besides, recent reports in animal and yeast cells suggest the existence of PM nanodomains that are independent of cholesterol and lipid phase and rely on anionic phospholipids as well as electrostatic protein/lipid interactions. Strikingly, we know very little on the role of anionic phospholipids in plant signaling. However, our preliminary data suggest that BKI1, an inhibitory protein of the steroid receptor kinase BRI1, interacts with various PIPs in vitro and is likely targeted to the PM by electrostatic interactions with these anionic lipids. These results open the possibility that BRI1, but also other receptor kinases, might be regulated by anionic phospholipids in plants. Here, we propose to analyze the function of anionic phospholipids in BRI1 signaling, using the root epidermis as a model system. First, we will ask what are the lipids that control membrane surface charge in this tissue and recruit BR-signaling component to the PM. Second, we will probe the presence of PIP-enriched nanodomains at the plant PM using super-resolution microscopy techniques and investigate the roles of these domains in BRI1 signaling. Finally, we will analyze the function of the BKI1-related plant-specific family of anionic phospholipid effectors in plant development. In summary, using a transversal approach ranging from in vitro studies to in vivo validation and whole organism physiology, this work will unravel the interplay between anionic phospholipids and receptor signaling in plants."

"In plants, receptor kinases form the largest family of plasma membrane (PM) receptors and they are involved in virtually all aspects of the plant life, including development, immunity and reproduction. In animals, key molecules that orchestrate the recruitment of signaling proteins to membranes are anionic phospholipids (e.g. phosphatidylinositol phosphate or PIPs). Besides, recent reports in animal and yeast cells suggest the existence of PM nanodomains that are independent of cholesterol and lipid phase and rely on anionic phospholipids as well as electrostatic protein/lipid interactions. Strikingly, we know very little on the role of anionic phospholipids in plant signaling. However, our preliminary data suggest that BKI1, an inhibitory protein of the steroid receptor kinase BRI1, interacts with various PIPs in vitro and is likely targeted to the PM by electrostatic interactions with these anionic lipids. These results open the possibility that BRI1, but also other receptor kinases, might be regulated by anionic phospholipids in plants. Here, we propose to analyze the function of anionic phospholipids in BRI1 signaling, using the root epidermis as a model system. First, we will ask what are the lipids that control membrane surface charge in this tissue and recruit BR-signaling component to the PM. Second, we will probe the presence of PIP-enriched nanodomains at the plant PM using super-resolution microscopy techniques and investigate the roles of these domains in BRI1 signaling. Finally, we will analyze the function of the BKI1-related plant-specific family of anionic phospholipid effectors in plant development. In summary, using a transversal approach ranging from in vitro studies to in vivo validation and whole organism physiology, this work will unravel the interplay between anionic phospholipids and receptor signaling in plants."